Heme oxygenase-1 protects against vascular constriction and proliferation

被引：464
作者：
Duckers, HJ
Boehm, M
True, AL
Yet, SF
San, H
Park, JL
Webb, RC
Lee, ME
Nabel, GJ
Nabel, EG
机构：
[1] NHLBI, Vasc Biol Branch, NIH, Bethesda, MD 20892 USA
[2] NHLBI, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
[3] Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA
[4] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA
来源：
NATURE MEDICINE | 2001年 / 7卷 / 06期
关键词：
D O I：
10.1038/89068
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Heme oxygenase (HO-1, encoded by Hmox1) is an inducible protein activated in systemic inflammatory conditions by oxidant stress. Vascular injury is characterized by a local reparative process with inflammatory components, indicating a potential protective role for HO-1 in arterial wound repair. Here we report that HO-1 directly reduces vasoconstriction and inhibits cell proliferation during vascular injury. Expression of HO-1 in arteries stimulated vascular relaxation, mediated by guanylate cyclase and cGMP, independent of nitric oxide. The unexpected effects of HO-1 on vascular smooth muscle cell growth were mediated by cell-cycle arrest involving p21(Cip1). HO-1 reduced the proliferative response to vascular injury in vivo; expression of HO-1 in pig arteries inhibited lesion formation and Hmox1(-/-) mice produced hyperplastic arteries compared with controls. Induction of the HO-1 pathway moderates the severity of vascular injury by at least two adaptive mechanisms independent of nitric oxide, and is a potential therapeutic target for diseases of the vasculature.
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页码：693 / 698
页数：6
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